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. 1990 Mar-Apr;63(2):109–119.

Neural responses to antigenic challenges and immunomodulatory factors.

D Saphier 1, H Ovadia 1, O Abramsky 1
PMCID: PMC2589313  PMID: 2399739

Abstract

In studies designed to examine the effects of the immune system, recordings of multi-unit electrical activity (MUA) in the central nervous system were made in the preoptic area/anterior hypothalamus (POA/AH) and paraventricular nucleus (PVN) of rats, following sheep red blood cell (SRBC) immunization. Peak increases in POA/AH MUA were observed on the fifth day following SRBC sensitization, the day on which serum antibodies were first detected. A significant increase in paraventricular nucleus (PVN) MUA was also observed on the sixth day. These changes in POA/AH and PVN MUA were found to be associated with increased plasma corticosterone levels on day 8. Induction of a second immune response to SRBC evoked a POA/AH MUA increase of extended duration but reduced amplitude, while administration of the immunosuppressive drug, cyclophosphamide, prevented both antibody generation and any increases in POA/AH MUA. These data suggest that activation of the immune system may provide signals, in the form of chemical messengers, which are able to alter neural activity in some regions of the brain that are important in neuroendocrine regulatory mechanisms. Accordingly, intracerebroventricular injections of thymic humoral factor or alpha-interferon decreased POA/AH MUA, increased EEG synchronization, and decreased plasma levels of corticosterone. Histamine and interleukin 1 did not alter POA/AH MUA but decreased EEG synchronization and increased plasma levels of corticosterone.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abo T., Kawate T., Itoh K., Kumagai K. Studies on the bioperiodicity of the immune response. I. Circadian rhythms of human T, B, and K cell traffic in the peripheral blood. J Immunol. 1981 Apr;126(4):1360–1363. [PubMed] [Google Scholar]
  2. Adams F., Quesada J. R., Gutterman J. U. Neuropsychiatric manifestations of human leukocyte interferon therapy in patients with cancer. JAMA. 1984 Aug 17;252(7):938–941. [PubMed] [Google Scholar]
  3. Ader R., Cohen N. Behaviorally conditioned immunosuppression. Psychosom Med. 1975 Jul-Aug;37(4):333–340. doi: 10.1097/00006842-197507000-00007. [DOI] [PubMed] [Google Scholar]
  4. Bartrop R. W., Luckhurst E., Lazarus L., Kiloh L. G., Penny R. Depressed lymphocyte function after bereavement. Lancet. 1977 Apr 16;1(8016):834–836. doi: 10.1016/s0140-6736(77)92780-5. [DOI] [PubMed] [Google Scholar]
  5. Besedovsky H., Sorkin E., Felix D., Haas H. Hypothalamic changes during the immune response. Eur J Immunol. 1977 May;7(5):323–325. doi: 10.1002/eji.1830070516. [DOI] [PubMed] [Google Scholar]
  6. Besedovsky H., del Rey A., Sorkin E., Dinarello C. A. Immunoregulatory feedback between interleukin-1 and glucocorticoid hormones. Science. 1986 Aug 8;233(4764):652–654. doi: 10.1126/science.3014662. [DOI] [PubMed] [Google Scholar]
  7. DOUGHERTY T. F. Effect of hormones on lympatic tissue. Physiol Rev. 1952 Oct;32(4):379–401. doi: 10.1152/physrev.1952.32.4.379. [DOI] [PubMed] [Google Scholar]
  8. Dafny N., Prieto-Gomez B., Reyes-Vazquez C. Does the immune system communicate with the central nervous system? Interferon modifies central nervous activity. J Neuroimmunol. 1985 Jul;9(1-2):1–12. doi: 10.1016/s0165-5728(85)80002-3. [DOI] [PubMed] [Google Scholar]
  9. Di Renzo G. F., Schettini G., Preziosi P. Effects of some antineoplastic agents on plasma levels of corticosterone, prolactin and thyroid stimulating hormone. Arch Int Pharmacodyn Ther. 1977 Dec;230(2):324–329. [PubMed] [Google Scholar]
  10. Fast P. E., Hatfield C. A., Franz C. L., Adams E. G., Licht N. J., Merritt M. V. Effects of treatment with immunomodulatory drugs on thymus and spleen lymphocyte subpopulations and serum corticosterone levels. Immunopharmacology. 1982 Dec;5(2):135–155. doi: 10.1016/0162-3109(82)90045-5. [DOI] [PubMed] [Google Scholar]
  11. Felten D. L., Felten S. Y., Carlson S. L., Olschowka J. A., Livnat S. Noradrenergic and peptidergic innervation of lymphoid tissue. J Immunol. 1985 Aug;135(2 Suppl):755s–765s. [PubMed] [Google Scholar]
  12. Fontana A., Kristensen F., Dubs R., Gemsa D., Weber E. Production of prostaglandin E and an interleukin-1 like factor by cultured astrocytes and C6 glioma cells. J Immunol. 1982 Dec;129(6):2413–2419. [PubMed] [Google Scholar]
  13. Friedman R. M., Vogel S. N. Interferons with special emphasis on the immune system. Adv Immunol. 1983;34:97–140. doi: 10.1016/s0065-2776(08)60378-8. [DOI] [PubMed] [Google Scholar]
  14. Gery I., Waksman B. H. Potentiation of the T-lymphocyte response to mitogens. II. The cellular source of potentiating mediator(s). J Exp Med. 1972 Jul 1;136(1):143–155. doi: 10.1084/jem.136.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Geschwind N., Behan P. Left-handedness: association with immune disease, migraine, and developmental learning disorder. Proc Natl Acad Sci U S A. 1982 Aug;79(16):5097–5100. doi: 10.1073/pnas.79.16.5097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gillis S., Crabtree G. R., Smith K. A. Glucocorticoid-induced inhibition of T cell growth factor production. II. The effect on the in vitro generation of cytolytic T cells. J Immunol. 1979 Oct;123(4):1632–1638. [PubMed] [Google Scholar]
  17. Gisler R. H. Stress and the hormonal regulation of the immune response in mice. Psychother Psychosom. 1974;23(1-6):197–208. doi: 10.1159/000286643. [DOI] [PubMed] [Google Scholar]
  18. Janković B. D., Isaković K. Neuro-endocrine correlates of immune response. I. Effects of brain lesions on antibody production, Arthus reactivity and delayed hypersensitivity in the rat. Int Arch Allergy Appl Immunol. 1973;45(3):360–372. [PubMed] [Google Scholar]
  19. Kawate T., Abo T., Hinuma S., Kumagai K. Studies of the bioperiodicity of the immune response. II. Co-variations of murine T and B cells and a role of corticosteroid. J Immunol. 1981 Apr;126(4):1364–1367. [PubMed] [Google Scholar]
  20. Kazimierczak W., Diamant B. Mechanisms of histamine release in anaphylactic and anaphylactoid reactions. Prog Allergy. 1978;24:295–365. [PubMed] [Google Scholar]
  21. Korneva E. A. Electrophysiological analysis of brain reactions to antigen. Ann N Y Acad Sci. 1987;496:318–337. doi: 10.1111/j.1749-6632.1987.tb35784.x. [DOI] [PubMed] [Google Scholar]
  22. McCann S. M., Ono N., Khorram O., Kentroti S., Aguila C. The role of brain peptides in neuroimmunomodulation. Ann N Y Acad Sci. 1987;496:173–181. doi: 10.1111/j.1749-6632.1987.tb35763.x. [DOI] [PubMed] [Google Scholar]
  23. Monjan A. A., Collector M. I. Stress-induced modulation of the immune response. Science. 1977 Apr 15;196(4287):307–308. doi: 10.1126/science.557841. [DOI] [PubMed] [Google Scholar]
  24. Murphy P. A., Simon P. L., Willoughby W. F. Endogenous pyrogens made by rabbit peritoneal exudate cells are identical with lymphocyte-activating factors made by rabbit alveolar macrophages. J Immunol. 1980 May;124(5):2498–2501. [PubMed] [Google Scholar]
  25. Nakashima T., Hori T., Kuriyama K., Kiyohara T. Naloxone blocks the interferon-alpha induced changes in hypothalamic neuronal activity. Neurosci Lett. 1987 Dec 4;82(3):332–336. doi: 10.1016/0304-3940(87)90278-3. [DOI] [PubMed] [Google Scholar]
  26. Plotnikoff N. P., Murgo A. J., Miller G. C., Corder C. N., Faith R. E. Enkephalins: immunomodulators. Fed Proc. 1985 Jan;44(1 Pt 1):118–122. [PubMed] [Google Scholar]
  27. Roberts F., Calcutt C. R. Histamine and the hypothalamus. Neuroscience. 1983 Aug;9(4):721–739. doi: 10.1016/0306-4522(83)90264-6. [DOI] [PubMed] [Google Scholar]
  28. Saphier D., Abramsky O., Mor G., Ovadia H. Multiunit electrical activity in conscious rats during an immune response. Brain Behav Immun. 1987 Mar;1(1):40–51. doi: 10.1016/0889-1591(87)90005-5. [DOI] [PubMed] [Google Scholar]
  29. Saphier D., Feldman S. Effects of stimulation of the preoptic area on hypothalamic paraventricular nucleus unit activity and corticosterone secretion in freely moving rats. Neuroendocrinology. 1986;42(2):167–173. doi: 10.1159/000124269. [DOI] [PubMed] [Google Scholar]
  30. Saphier D., Kidron D., Ovadia H., Trainin N., Pecht M., Burstein Y., Abramsky O. Neurophysiological changes in the brain following central administration of immunomodulatory factors. Isr J Med Sci. 1988 Apr-May;24(4-5):261–263. [PubMed] [Google Scholar]
  31. Shek P. N., Sabiston B. H. Neuroendocrine regulation of immune processes: change in circulating corticosterone levels induced by the primary antibody response in mice. Int J Immunopharmacol. 1983;5(1):23–33. doi: 10.1016/0192-0561(83)90068-1. [DOI] [PubMed] [Google Scholar]
  32. Smedley H., Katrak M., Sikora K., Wheeler T. Neurological effects of recombinant human interferon. Br Med J (Clin Res Ed) 1983 Jan 22;286(6361):262–264. doi: 10.1136/bmj.286.6361.262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Smith E. M., Blalock J. E. Human lymphocyte production of corticotropin and endorphin-like substances: association with leukocyte interferon. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7530–7534. doi: 10.1073/pnas.78.12.7530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Solomon G. F. Psychoneuroimmunology: interactions between central nervous system and immune system. J Neurosci Res. 1987;18(1):1–9. doi: 10.1002/jnr.490180103. [DOI] [PubMed] [Google Scholar]
  35. Solomon G. F. Stress and antibody response in rats. Int Arch Allergy Appl Immunol. 1969;35(1):97–104. doi: 10.1159/000230163. [DOI] [PubMed] [Google Scholar]
  36. Swanson L. W., Sawchenko P. E., Rivier J., Vale W. W. Organization of ovine corticotropin-releasing factor immunoreactive cells and fibers in the rat brain: an immunohistochemical study. Neuroendocrinology. 1983;36(3):165–186. doi: 10.1159/000123454. [DOI] [PubMed] [Google Scholar]
  37. Sztein M. B., Vogel S. N., Sipe J. D., Murphy P. A., Mizel S. B., Oppenheim J. J., Rosenstreich D. L. The role of macrophages in the acute-phase response: SAA inducer is closely related to lymphocyte activating factor and endogenous pyrogen. Cell Immunol. 1981 Sep 1;63(1):164–176. doi: 10.1016/0008-8749(81)90037-x. [DOI] [PubMed] [Google Scholar]
  38. Trainin N., Handzel Z. T., Pecht M. Biological and clinical properties of THF. Thymus. 1985;7(3):137–150. [PubMed] [Google Scholar]
  39. Wertman E., Ovadia H., Feldman S., Abramsky O. Prevention of experimental allergic encephalomyelitis by anterior hypothalamic lesion in rats. Neurology. 1985 Oct;35(10):1468–1470. doi: 10.1212/wnl.35.10.1468. [DOI] [PubMed] [Google Scholar]

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